trifluridine/tipiracil combined with cetuximab in the treatment of third-line and above ras/braf wild-type mcrc

Conditions: Colorectal Cancer Metastatic

Summary: this study is a single-center, prospective, single-arm exploratory study aimed at evaluating the efficacy and safety of trifluridine/tipiracil in combination with cetuximab in the treatment of third-line and above ras/braf wild-type metastatic colorectal cancer.


Eligibility criteria:
inclusion criteria: 1. patient able and willing to provide written informed consent and to comply with the study protocol and follow-up inspection. 2. histologically or cytologically confirmed metastatic adenocarcinoma of the colon; excluding appendiceal and anal canal cancers. 3. previously received at least second-line treatment, including two standard treatment regimens (such as fluoropyrimidine, capecitabine, irinotecan, oxaliplatin with or without anti-vegf or anti-egfr agents), if previously received first-line anti-egfr therapy, achieving at least a partial response (pr) or above, with a discontinuation interval of at least one year. 4. eastern cooperative oncology group (ecog) performance status of 0-1. 5. measurable disease by computed tomography (ct) or magnetic resonance imaging (mri) (based on recist 1.1 criteria, with the longest diameter of tumor lesions on ct/mri scan ≥10mm, and the shortest diameter of lymph node lesions on ct/mri scan ≥15mm). 6. wild-type ras/braf gene detected. 7. able to take oral medication. 8. normal organ function, meeting the following criteria within 14 days before treatment initiation: * neutrophil count ≥1.5×10\^9/l; * platelet count ≥75×10\^9/l; * hemoglobin ≥9.0g/dl; * aspartate aminotransferase (ast) ≤2.5×upper limit of normal (uln) (or ≤5×uln if liver metastases); * alanine aminotransferase (alt) ≤2.5×uln (or ≤5×uln if liver metastases); * total bilirubin ≤1.5×uln; * creatinine clearance (calculated by cockcroft and gault formula) \>60ml/min or serum creatinine ≤1.5×uln; 9. expected survival time \>3 months (90 days). 10. women of childbearing potential must have used reliable contraception for 7 days prior to enrollment, have had a negative pregnancy test, and agree to use appropriate contraception methods during the trial and for 6 months after the last dose of investigational drug. men must agree to use appropriate contraception methods or have undergone surgical sterilization during the trial and for 6 months after the last dose of investigational drug. exclusion criteria: 1. prior treatment with trifluridine/tipiracil; 2. patients with known dmmr or msi-h advanced colorectal cancer who have not previously received anti-pd-1 or pd-l1 inhibitors; 3. participation in another drug clinical trial or receipt of systemic chemotherapy, radiotherapy, or biologic therapy within the past 4 weeks; 4. known or suspected brain metastases; 5. synchronous or metachronous cancer with a disease-free survival of ≥5 years (except for colorectal cancer) excluding cured or curatively treated mucosal cancers (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.); 6. factors significantly affecting oral drug absorption, such as dysphagia, chronic diarrhea, and gastrointestinal obstruction; uncontrolled crohn's disease or ulcerative colitis; 7. symptomatic malignant effusion requiring symptomatic treatment (including pleural effusion, ascites, pericardial effusion); 8. pregnant or lactating women; patients with reproductive potential unwilling or unable to use effective contraceptive measures; 9. known allergy to the investigational drug, drug class, or its components; 10. requirement for systemic corticosteroid therapy (excluding local steroids and cetuximab pre-treatment); 11. history of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or radiographic evidence of interstitial lung disease; 12. active local or systemic infections requiring treatment; 13. new york heart association (nyha) functional classification ≥ii or severe heart disease; 14. known human immunodeficiency virus (hiv) infection or acquired immunodeficiency syndrome (aids) or history of active hepatitis b or hepatitis c; 15. unresolved toxicity (ctcae\>grade 1) or incomplete recovery from previous cancer surgery. 16. patients deemed unsuitable for the study by the investigator.

Keywords: ras/braf wild-type